Interleukin 2 (IL-2) has demonstrated a potent ability to augment natural killer (NK) activity and to generate killer cells against NK- insensitive targets and secrete interferon-gamma (IFN-gamma) by LGL. A project is being conducted to investigate IFN gene expression and regulation in highly-purified human large granular lymphocytes (LGLs) and T cells. IL-2 treatment of freshly isolated human LGLs rapidly induces IFN-gamma mRNA and protein is secreted in the culture medium. Because of this one signal activation of cytokine genes, the CD3- LGL represents an excellent cell type to study signal transduction leading to both modulation of cytotoxicity and gene transcription, since it represents a cell type "poised" for activation and is capable of responding to a single stimulus. CD16 expression on NK cells is being utilized to examine signal transduction pathways in comparison to TcR events in T cells. Present studies involve examining agents that modulate signal transduction events, with an emphasis on understanding the mechanism of action of biologicals and defining the specific surface receptors involved.